Are critical groups of children being left out of NIH research? That's what 50 members of Congress want to know.
A bipartisan group of lawmakers recently sent NIH Director Francis Collins a letter raising concerns about the agency's ability to adequately track whether children are appropriately included in all the relevant clinical trials it sponsors.
Although NIH policy has required the inclusion of children in research since fiscal 1996, the agency's current grant application process only asks whether people younger than 21 will be included in the proposed project. That leaves grant reviewers "little information with which to differentiate between meaningful pediatric representation and negligible inclusion of 18 to 20 year olds," the lawmakers said.
The letter also points out that while the NIH's Research, Condition and Disease Categorization (RCDC) system classifies some research as pediatric in nature, it can't determine whether such research includes children from underrepresented age groups such as neonates and infants. Another problem with the RCDC system is that it can't show whether adult research inappropriately excludes children.
"We are concerned that this lack of tracking leaves the NIH unable to answer questions about whether children are appropriately included in trials pertinent to them," the letter said.
The lawmakers asked the NIH to describe how it monitors implementation of its pediatric inclusion policy and tracks whether children are appropriately enrolled in relevant trials. They also asked the agency to explain why it doesn't collect age demographics in trial enrollment as it does for race, ethnicity and gender.
Meanwhile, the FDA issued a draft guidance on general clinical pharmacology considerations to help sponsors identify an appropriate dose for pediatric trials. The draft, which was published in the Federal Register Tuesday, also describes using quantitative approaches, such as pharmacometrics, to employ disease and exposure-response knowledge from prior clinical studies to design and evaluate pediatric studies. Comments on the guidance are due Feb. 7.
In the wake of the guidance, the FDA is convening the Pediatric Oncologic Subcommittee of its Oncologic Drugs Advisory Committee Thursday to discuss the diseases to be studied, pediatric patient populations to be included and possible study designs in the development of the following products for pediatric use:
• Synta Pharmaceuticals Corp.'s ganetespib. A small-molecule inhibitor of heat-shock protein 90, ganetespib has been or is currently being evaluated in adult trials against a variety of cancers, including sarcoma, acute myeloid leukemia (AML), and non-small-cell lung, breast, endometroid, ovarian, fallopian tube and peritoneal cancers. In preclinical models, it has shown activity in several cancers relevant to pediatrics such as synovial sarcoma, Ewing sarcoma, osteosarcoma, malignant peripheral nerve sheath tumor (MPNST) and rhabdomyosarcoma. A small, ongoing phase I/II trial is evaluating ganetespib in combination with sirolimus in older adolescent and adult patients with refractory sarcoma with a focus on MPNST. (See BioWorld Today, July 23, 2014.)
• Nektar Therapeutics Inc.'s NKTR-102 (etirinotecan pegol). A polyethylene glycol conjugate prodrug of irinotecan, etirinotecan has been evaluated in more than 1,000 adult patients with solid tumors in 10 clinical trials, four of which are ongoing. (See BioWorld Today, Aug. 22, 2014.)
• Roche AG's RO5503781. A small-molecule inhibitor of the murine double minute 2 protein, Roche's candidate is in dose-finding studies in adult patients with solid tumors and AML. A few months ago, the EMA's Paediatric Committee issued a positive opinion for Roche's proposed pediatric investigation plan, which includes a dose-finding safety study in children with relapsed or refractory solid tumors or acute leukemia followed by a confirmatory trial.
BIOSIMILAR COMPROMISE PROPOSED
Even though the FDA has yet to release guidance on the development of interchangeable biosimilars that could be automatically substituted for the prescribed reference biologic, controversy has brewed over proposed state laws allowing that substitution at the pharmacy.
In the past, the Generic Pharmaceuticals Association (GPhA) bristled at a legislative model, supported by the Biotechnology Industry Organization and innovator drugmakers, that would require pharmacists to notify physicians if an interchangeable biosimilar were dispensed. While several generic drugmakers saw such legislation as an impediment to automatic substitution, others said it was necessary for pharmacovigilance. (See BioWorld Today, Feb. 5, 2014.)
Now GPhA is supporting compromise legislation that would require notification regardless of whether a pharmacist dispenses the reference biologic or an interchangeable. Under the compromise statute, pharmacies would have to tell the prescriber, within a reasonable time, which biologic was given to the patient, identifying it by product name and manufacturer.
The only exceptions to the notification requirement would be if there is no FDA-approved interchangeable for the biologic prescribed or a prescription is refilled with the same product previously dispensed.
GPhA expects the compromise legislation to be introduced in many states next year, as each state must have a law in place to allow automatic biologic substitution. While Congress gave the FDA the authority to approve both biosimilars and interchangeable biologics in 2010, whether, and how, pharmacy substitution is allowed is up to state law.
EBOLA VACCINES GET BOOST
Sponsors of three vaccines under development for Ebola received immunity Tuesday from U.S. legal claims related to the manufacturing, testing, development and use of the vaccines.
Via a declaration under the Public Readiness and Emergency Preparedness (PREP) Act, Health and Human Services Secretary Sylvia Burwell extended the protection to Glaxosmithkline plc's ChAd3-EBO-Z vaccine, Bioprotection Services Corp.'s BPSC1001 vaccine and Janssen Corp.'s Ad26.ZEBOV/MVA-BN-Filo vaccine.
The declaration is intended to strengthen the incentive to develop the potential use of the products in large-scale vaccination campaigns in West Africa. While it provides legal protection under U.S. law, the declaration doesn't necessarily provide immunity for a claim brought outside the U.S.
In using the PREP Act for the vaccines, Burwell hoped other countries would follow suit, enacting appropriate liability protection and compensation legislation. "As a global community, we must ensure that legitimate concerns about liability do not hold back the possibility of developing an Ebola vaccine, an essential strategy in our global response to the Ebola epidemic in West Africa," Burwell said.
PCORI TO FUND HCV RESEARCH
Driven by what it considered the lack of real-world evidence of the long-term effectiveness of new hepatitis C virus (HCV) drugs and a dearth of comparative evidence to help inform decisions about screening, diagnosis and treatment of HCV, the board of governors for the Patient-Centered Outcomes Research Institute (PCORI) voted Monday to approve up to $50 million in grants for HCV comparative clinical effectiveness research (CER) studies.
The funding announcement will provide for up to four CER studies that will assess screening methods and testing strategies that lead to the best HCV detection rates, consider alternative ways to deliver care to high-risk populations, explore the trade-offs between long-term virologic response and adverse effects associated with different regimens of new oral antiviral medications, and compare the benefits and harms of starting treatment immediately after an HCV diagnosis vs. active surveillance, in which treatment starts when a patient progresses to liver disease or other manifestations of infection.
The board also approved two funding announcements, totaling up to $150.7 million, for the second phase development of PCORnet, an initiative to improve health research nationwide through the use of data from electronic health records and other sources.